Occlusion perfusion catheter

ABSTRACT

Catheters for occluding, visualizing, irrigating, evacuating, and delivering agents to a treatment area are disclosed. The catheters comprise a catheter body comprising five lumens, first and second occlusion balloons coupled to the catheter body, an optional space-occupying balloon coupled to the catheter body and disposed between the first and second occlusion balloons, and an optional visualization means that enables visualization between the first and second occlusion balloons. Methods for using these catheters are also disclosed. A method comprises inflating the first and second occlusion balloons, inflating the space-occupying balloon, allowing fluid to exit via an evacuation lumen, optionally irrigating or aspirating to facilitate fluid exit via said lumen, and delivering an agent to a treatment area via the agent lumen.

CROSS-REFERENCE TO RELATED APPLICATIONS

This Non-Provisional Patent Application, filed under 35 U.S.C. §111(a),claims the benefit under 35 U.S.C. §119(e)(1) of U.S. Provisional PatentApplication No. 61/110,744, filed under 35 U.S.C. §111(b) on 3 Nov.2008, and which is hereby incorporated by reference in its entirety.

BACKGROUND

1. Field

The present disclosure relates generally to catheter devices and methodsfor the site-specific delivery of agents to biological spaces in medicalprocedures. More particularly, the present disclosure relates tocatheter devices comprising multiple inflatable means carried by thecatheters, with at least one radial opening located between at least apair of inflatable means. The present disclosure also relates to methodsfor site-specific delivery of agents into blood vessels (including theblood vessel lumen and the vessel wall) for treatment of said bloodvessels and/or other organ systems, as well as methods of visualizingthe lumen of said blood vessels and/or other organ systems.

2. Description of Related Art

Regardless of the interventional treatment utilized to maintain vesselpatency in vascular disease, there will always be restenosis and/orocclusions. The reason for this is that all of these treatmentmodalities create an intentional “controlled injury” of the vessel wall.In the healing process of this injury, neointimal hyperplasia (a form ofscar tissue) develops. It develops because some of the cells of thevessel wall have been damaged, become “angry” (inflamed) and causesproliferation and migration of muscle cells from the media of the vesselwall into the lumen of the vessel. This process is called neointimalhyperplasia. The commonly-accepted method of controlling the developmentof neointimal hyperplasia is to treat it at the cellular level. Theseproliferating cells need the ability to function as normal cells and notbecome “angry”. This can be accomplished by treating this “controlledinjury” at the cellular level utilizing biopharmaceuticals, conventionalsmall-molecule pharmaceuticals, live cells, or other new therapies(referred to collectively herein as “therapeutic agents” or simply“agents”). Pharmaceutical and other companies are gearing up to developthese live cells and therapies. This live cell technology has to bedelivered locally to the area of “controlled injury” of the media of thevessel wall. Such therapies are particularly susceptible toenvironmental factors inherent to the delivery process, such as fluidpressure and shear stress, and devices of the prior art do not addressthese factors adequately.

Pharmaceutical companies have developed, or have the ability to develop,pharmaceuticals that will also affect proliferation and migration ofthese cells. The problem is that most or all of these have the potentialto be toxic when given systemically. However, when applied regionally toa localized area of “controlled injury” (e.g., in “controlled” ordiscrete amounts), these agents have the potential of being effective,but non-toxic (or at least significantly less toxic).

The technical problem underlying the present disclosure was therefore toovercome these prior art difficulties by creating devices providing forcontrolled, focal delivery and subsequent aspiration of therapeuticagents. The solution to this technical problem is provided by theembodiments characterized in the claims.

BRIEF SUMMARY

The present disclosure provides an improved agent delivery catheter thatobviates the above-mentioned limitations, and further provides methodsof using the same. The catheter provides a vehicle for local delivery ofany of the aforementioned forms of therapy to a site of injury, as wellas means for visualizing said site.

The catheter is a five-lumen catheter designed with at least twoocclusion balloons, one proximal and one distal.

In one embodiment, a space-occupying balloon is provided between the twoocclusion balloons, to occupy space, so producing an occlusion-perfusioncatheter, or “OPC.” When the space-occupying balloon is present andinflated, the result is a volume of space between the space occupyingballoon, the two occlusion balloons, and the vessel wall—the area ofcontrolled injury (the “treatment region”). In other words, the volumeof said space is less than when the space-occupying balloon is eitherabsent or is deflated. Pharmaceuticals, live cells, etc. (“agents”) canthen be injected into said space surrounding the balloons and bounded bythe vessel wall. The agents can be perfused through the area(s) ofcontrolled injury and optionally further forced into the media of thevessel wall via elevated fluid pressure (elevated pressure within thetreatment region). The agent can then be aspirated as well, which may beimportant if toxic agents are used. The agent can be aspirated via thesame catheter lumen used to inject the agent and/or via a separatededicated catheter lumen. The intended result is to minimize restenosisof the vessel. Because an agent can be introduced into the treatmentregion via one catheter lumen and aspirated via a different catheterlumen, one may “flush” the treatment region if such is desired (e.g.,with saline).

In one embodiment, a fiber optic device or other means known to those ofordinary skill in the art may be incorporated into the catheter topermit illumination and remote visualization of the treatment region(“visualization means”), so producing an occlusion-visualizationcatheter, or “OVC.” In this embodiment, comprising visualization means,the space-occupying balloon is absent. Pharmaceuticals, live cells, etc.(“agents”) can then be injected—via a dedicated catheter lumen—into thetreatment region. The agents can be perfused through the area(s) ofcontrolled injury and optionally further forced into the media of thevessel wall via elevated fluid pressure. The agent can then be aspiratedas well, which may be important if toxic agents are used. The agent canbe aspirated via the same catheter lumen used to inject the agent and/orvia a separate dedicated catheter lumen. The intended result is tominimize restenosis of the vessel. Because an agent can be introducedinto the treatment region via one catheter lumen and aspirated via adifferent catheter lumen, one may “flush” the treatment region if suchis desired (e.g., with saline). By flushing the treatment region, onemay improve visualization of the treatment region.

The device comprises a five-lumen extrusion, two occlusion balloons, aguide wire lumen, a perfusion lumen, an evacuation lumen, a ballooninflation hub, a therapeutic agent perfusion/evacuation/guide wire hubthat allow selective access to the various lumens, and eithervisualization means, or a space occupying balloon. The purposes andfunctions of the five lumens are as follows: (a) guide wire lumen—allowsthe catheter to track over guide wire to treatment site; (b) spaceoccupying balloon inflation lumen—allows inflation/deflation control ofspace occupying balloon, or provides passage for visualization means;(c) therapeutic agent perfusion lumen—allows access to treatment regionfor perfusion of therapeutic agent; (d) occlusion balloon inflationlumen—allows simultaneous inflation/deflation control of occlusionballoons; and (e) evacuation lumen—allows evacuation of or exit pathfrom treatment region for therapeutic agent, or a second, individuallycontrolled perfusion lumen for two-part therapeutic agents.

The two occlusion balloons, one distal and one proximal, define thetreatment region (the area of controlled injury) as the volume containedbetween them. When present, the optional space occupying balloon allowsadjustment of the treatment region volume (the volume between the twoocclusion balloons) by simply adjusting the fill volume of the spaceoccupying balloon. In other words, by inflating the space occupyingballoon, less therapeutic agent is required to be delivered to thetreatment region between the two occlusion balloons than would berequired if the space occupying balloon were not inflated (or wereabsent entirely, as when the visualization means is provided).

In all cases, the OPC or OVC is delivered to the treatment site via aminimally invasive insertion technique (for example, the Seldingertechnique). The applicants anticipate an “over the wire” or “rapidexchange” (i.e. “monorail”) type of delivery, which are the two typicalmethods in use by interventional radiologists, cardiologists, andvascular surgeons, not to mention other medical specialists. It will beunderstood by those of ordinary skill in the art that other methods ofdelivery may be employed that keep within the spirit of the disclosureof the device and the method.

The present disclosure provides, in one embodiment, a five-lumencatheter comprising: a catheter shaft comprising a distal end and aproximal end, the distal end having a shaft distal tip; a first balloonpositioned on the shaft proximal to the shaft distal tip; a secondballoon positioned on the shaft proximal to the first balloon; an agentdelivery segment positioned on the shaft between the first and secondballoons, distal to the second balloon, and having one orifice (theagent delivery segment skive) formed therein; an aspiration segmentpositioned on the shaft between the first and second balloons, proximalto the first balloon, and having one orifice (the aspiration segmentskive) formed therein; visualization means positioned between the firstand second balloons; a balloon inflation hub coupled to the shaftproximal end; a therapeutic agent perfusion/evacuation/guide wire hubcoupled to the balloon inflation hub; and a guidewire lumen formedwithin the shaft and in communication with an opening formed in thedistal end of the catheter and with an opening formed in the proximalend of the catheter. As will be appreciated by those of ordinary skillin the art, the aspiration segment may be positioned on the shaftbetween the first and second balloons and proximal to the agent deliverysegment, or between the first and second balloons and distal to theagent delivery segment.

The present disclosure provides, in one embodiment, a five-lumencatheter comprising: a catheter shaft comprising a distal end and aproximal end, the distal end having a shaft distal tip; a first balloonpositioned on the shaft proximal to the shaft distal tip; a secondballoon positioned on the shaft proximal to the first balloon; a thirdballoon positioned on the shaft proximal to the second balloon; an agentdelivery segment positioned on the shaft between the second and thirdballoons and having one orifice formed therein; an aspiration segmentpositioned on the shaft between the first and second balloons and havingone orifice formed therein; a balloon inflation hub coupled to the shaftproximal end; a therapeutic agent perfusion/evacuation/guide wire hubcoupled to the balloon inflation hub; and a guidewire lumen formedwithin the shaft and in communication with an opening formed in thedistal end of the catheter and with an opening formed in the proximalend of the catheter. As will be appreciated by those of ordinary skillin the art, the aspiration segment may be positioned on the shaftbetween the first and second balloons with the agent delivery segmentpositioned between the second and third balloons, or the aspirationsegment may be positioned between the second and third balloons with theagent delivery segment positioned between the first and second balloons.Either of these arrangements are within the scope of the presentdisclosure.

In further embodiments, the catheters of the present disclosureoptionally comprise a first pressure sensing means, whereby the pressureof the fluid environment at or near the agent delivery segment can bemeasured, known, or estimated. In this context, the term “fluid”indicates a continuous amorphous substance whose molecules and anysuspended or dispersed components (e.g., cells, amino acids,polypeptides, nucleic acids, polynucleotides, vehicles, liposomes,micelles, nanoparticles, and combinations thereof) move freely past oneanother, has the tendency to assume the shape of its container (e.g., aliquid), and that is capable of flowing. It includes therapeutic agentsinjected via the device of the present disclosure, including but notlimited to: solutions, drugs or other therapeutic agents dissolved insolution; cells suspended in solution; proteins dissolved or suspendedin solution; nucleic acids dissolved or suspended in solution; vehicles(e.g., liposomes, micelles, vectors, nanoparticles, phospholipiddispersions, lamellar layers, liquid crystals, etc.); and combinationsthereof. In this embodiment, the therapeutic agentperfusion/evacuation/guide wire hub further comprises a pressure sensorconnector. The first pressure sensing means is contained at least partlywithin the agent perfusion lumen, and comprises a proximal and a distalend, where the distal end is located at or near the agent deliverysegment skive and the proximal end is coupled to the pressure sensorconnector.

In further embodiments, the OPC and OVC catheters of the presentdisclosure optionally comprise a second pressure sensing means (eitherindependently of or together with the first pressure sensing meansdescribed above), having a proximal and a distal end, whereby thepressure of the fluid environment within the therapeutic agent perfusionlumen—at or near the perfusion skive—can be known or estimated. In thisaspect, the second pressure sensing means may be located alongside theproximal end of the first pressure sensing means, with the secondpressure sensing means proximal end also located at the pressure sensorconnector, but with the second pressure sensing means distal end locatedwithin the therapeutic agent perfusion lumen at or near the perfusionskive. Without intending to be bound to a particular pressure sensor, anexample of a pressure sensor suitable for this embodiment is the FOP-MIV(Sequoia Technology, Ltd.; Reading, UK)—a fiber optic pressure sensor.

In further embodiments, the catheters of the present disclosureoptionally comprise a first two- or three-way valve or check valve influid communication with the perfusion port and the therapeutic agentdelivery lumen so that fluid may be delivered—but not aspirated—via theagent delivery segment. In related embodiments, the catheters of thepresent disclosure optionally comprise a second two- or three-way valveor check valve in fluid communication with the aspiration port and theaspiration lumen so that fluid may be aspirated—but not delivered—viathe aspiration segment. In preferred embodiments, the catheters of thepresent disclosure optionally comprise a first two- or three-way valveor check valve in fluid communication with the perfusion port and thetherapeutic agent delivery lumen, and a second two- or three-way valveor check valve in fluid communication with the aspiration port and theaspiration lumen. The optional first and/or second two- or three-wayvalve or check valves may be present either independently of or togetherwith the first pressure sensing means described above and/or the secondpressure sensing means described above.

Disclosed herein is a catheter comprising: a catheter shaft having adistal end having a shaft distal tip and a proximal end; a first balloonpositioned on the shaft proximal to the shaft distal tip; a secondballoon positioned on the shaft proximal to the first balloon; a thirdballoon positioned on the shaft proximal to the second balloon; an agentdelivery segment positioned on the shaft between the first and thirdballoons and having one orifice formed therein; an aspiration segmentpositioned on the shaft between the first and third balloons and havingone orifice formed therein; and a guidewire lumen formed within theshaft and in communication with: an opening formed in a proximal end ofthe catheter; and an opening formed in a distal end of the catheter.

In one embodiment, the catheter may further comprise a firstpressure-sensing means having proximal and distal ends and a lengththerebetween, wherein said distal end is at or near the agent deliverysegment orifice. Furthermore, said first pressure-sensing means proximalend is in communication with a connector formed on the proximal end ofthe catheter shaft.

In one embodiment, the catheter may further comprise a first inflationlumen in communication with the first and third balloons. The firstinflation lumen may be further in communication with a first ballooninflation port formed on the proximal end of the catheter shaft.

In one embodiment, the catheter may further comprise a second inflationlumen in communication with the second balloon. Furthermore, the secondinflation lumen may be further in communication with a second ballooninflation port formed on the proximal end of the catheter shaft.

In one embodiment, the catheter may further comprise an aspiration lumenin communication with the aspiration segment orifice. Furthermore, theaspiration lumen may be further in communication with an aspiration portformed on the proximal end of the catheter shaft.

In one embodiment, the catheter may further comprise a valve incommunication with said aspiration port.

In one embodiment, the catheter may further comprise an agent deliverylumen in communication with the agent delivery segment orifice.Furthermore, the agent delivery lumen may be further in communicationwith an agent delivery port formed on the proximal end of the cathetershaft.

In one embodiment, the catheter may further comprise a firstpressure-sensing means having proximal and distal ends and a lengththerebetween, wherein said first pressure-sensing means proximal end isin communication with a connector formed on the proximal end of thecatheter shaft and said first pressure-sensing means distal end is at ornear the agent delivery segment orifice.

In one embodiment, the catheter may further comprise a secondpressure-sensing means having proximal and distal ends and a lengththerebetween, wherein said second pressure-sensing means proximal end isin communication with the connector formed on the proximal end of thecatheter shaft and said second pressure-sensing means distal end islocated within the agent delivery lumen.

Also disclosed herein is a catheter comprising: a catheter shaft havinga distal end having a shaft distal tip and a proximal end; a firstballoon positioned on the shaft proximal to the shaft distal tip, asecond balloon positioned on the shaft proximal to the first balloon,and a third balloon positioned on the shaft proximal to the secondballoon; a first inflation lumen in communication with the first andthird balloons, wherein said first inflation lumen is further incommunication with a first balloon inflation port formed on the proximalend of the catheter shaft; a second inflation lumen in communicationwith the second balloon, wherein said second inflation lumen is furtherin communication with a second balloon inflation port formed on theproximal end of the catheter shaft; an agent delivery segment positionedon the shaft between the second and third balloons and having oneorifice formed therein, wherein the agent delivery lumen is incommunication with the agent delivery segment orifice and an agentdelivery port formed on the proximal end of the catheter shaft; anaspiration segment positioned on the shaft between the first and secondballoons and having one orifice formed therein, wherein the aspirationlumen is in communication with the aspiration segment orifice and anaspiration port formed on the proximal end of the catheter shaft, saidaspiration port optionally further comprising a valve in communicationwith the aspiration port; a guidewire lumen formed within the shaft andin communication with an opening formed in a proximal end of thecatheter and an opening formed in a distal end of the catheter; a firstpressure-sensing means having proximal and distal ends and a lengththerebetween, wherein said first pressure-sensing means proximal end isin communication with a connector formed on the proximal end of thecatheter shaft and said first pressure-sensing means distal end is at ornear the agent delivery segment orifice; and a second pressure-sensingmeans having proximal and distal ends and a length therebetween, whereinsaid second pressure-sensing means proximal end is in communication withthe connector formed on the proximal end of the catheter shaft and saidsecond pressure-sensing means distal end is located within the agentdelivery lumen.

Also described herein is a catheter comprising: a catheter shaft havinga distal end having a shaft distal tip and a proximal end; a firstballoon positioned on the shaft proximal to the shaft distal tip; asecond balloon positioned on the shaft proximal to the first balloon; anagent delivery segment positioned on the shaft between the first andsecond balloons and having one orifice formed therein; an aspirationsegment positioned on the shaft between the first and second balloonsand having one orifice formed therein; a visualization means, whereinsaid visualization means enables visualization between the first andsecond balloons; and a guidewire lumen formed within the shaft and incommunication with: an opening formed in a proximal end of the catheter;and an opening formed in a distal end of the catheter. In oneembodiment, the catheter may further comprise a first inflation lumen incommunication with the first and second balloons, wherein said firstinflation lumen is further in communication with a first ballooninflation port formed on the proximal end of the catheter shaft. In oneembodiment, the catheter may further comprise a visualization meanslumen in communication with a visualization means slot and containing atleast a portion of said visualization means. In one embodiment, thecatheter may further comprise an aspiration lumen in communication withthe aspiration segment orifice, wherein said aspiration lumen is furtherin communication with an aspiration port formed on the proximal end ofthe catheter shaft. In one embodiment, the catheter may further comprisean agent delivery lumen in communication with the agent delivery segmentorifice wherein said agent delivery lumen is further in communicationwith an agent delivery port formed on the proximal end of the cathetershaft.

BRIEF DESCRIPTION OF THE DRAWINGS

For a further understanding of the nature, objects, and advantages ofthe devices and methods of the present disclosure, reference should behad to the following detailed description, read in conjunction with thefollowing drawings, wherein like reference numerals denote likeelements.

FIG. 1 shows a side elevational view of one embodiment of a catheter ofthe present disclosure. For clarity, the entire device has not beenshown and the figure is not drawn to scale. The jagged line M-Mrepresents a break in the continuum of the catheter.

FIG. 2 is a perspective view of one embodiment of a catheter of thepresent disclosure in its assembled form.

FIG. 3 is a cross-sectional view taken along line B-B as shown in FIG.1, displaying a distal occluding balloon, five lumens which may beemployed to inflate and deflate balloons or deliver and removetherapeutic agents or biologic samples, and a skive port extendingthrough the thickness of the catheter wall such that occluding ballooninflation lumen of the catheter is in communication with the catheterexterior wall for inflating and deflating the distal occluding balloon.

FIG. 4 is a cross-sectional view taken along line C-C as shown in FIG.1, displaying five lumens which may be employed to inflate and deflateballoons or to deliver and remove therapeutic agents, and an aspirationskive port extending through the thickness of the catheter wall suchthat aspiration lumen of the catheter is in communication with thecatheter exterior wall for aspirating therapeutic agents or fluidsamples from the lumen of a blood vessel.

FIG. 5 is a cross-sectional view taken along line D-D as shown in FIG.1, displaying a space occupying balloon, five lumens which may beemployed to inflate and deflate balloons or to deliver and removetherapeutic agents, and a skive port extending through the thickness ofthe catheter wall such that space-occupying balloon inflation lumen ofthe catheter is in communication with the catheter exterior wall forinflating and deflating the space occupying balloon.

FIG. 6 is a cross-sectional view taken along line E-E as shown in FIG.1, displaying five lumens which may be employed to inflate and deflateballoons or to deliver and remove therapeutic agents, and a skive portextending through the thickness of the catheter wall such thattherapeutic agent delivery lumen of the catheter is in communicationwith the catheter exterior wall for delivering therapeutic agents to thelumen of a blood vessel.

FIG. 7 is a cross-sectional view taken along line F-F as shown in FIG.1, displaying a proximal occluding balloon, five lumens which may beemployed to inflate and deflate balloons or to deliver and removetherapeutic agents, and a skive port extending through the thickness ofthe catheter wall such that occluding balloon inflation lumen of thecatheter is in communication with the catheter exterior wall forinflating and deflating the proximal occluding balloon.

FIG. 8 is a side view of the catheter assembly of the presentdisclosure, showing the therapeutic agent perfusion/aspiration andguidewire hub (the “perfusion/aspiration hub”) in a plane perpendicularto the balloon inflation hub.

FIG. 9 is a cross-sectional side view of the balloon inflation hub ofthe present disclosure, taken along the line H-H, as shown in FIG. 8.For the sake of clarity, the therapeutic agent perfusion/aspiration andguidewire hub is not shown in this FIG. 9.

FIG. 10 is a side view of the catheter assembly of the presentdisclosure, showing the balloon inflation hub in a plane perpendicularto the therapeutic agent perfusion/aspiration and guidewire hub.

FIG. 11 is a cross-sectional side view of therapeutic agentperfusion/aspiration and guidewire hub of the present disclosure, takenalong the line G-G, as shown in FIG. 10. For the sake of clarity, theballoon inflation hub is not shown in this FIG. 11.

FIGS. 12A and 12B show an embodiment of an aspect of a catheter of thepresent disclosure which has been inserted into a blood vessel. Forclarity, the entire device has not been shown and the figure is notdrawn to scale. FIG. 12A shows the distal portion of the catheter of thepresent disclosure with the distal and proximal occluding balloonsinflated, and the space occupying balloon deflated. FIG. 12B shows theresult of inflating space occupying balloon.

FIG. 13 is a plan view of a catheter assembly of the present disclosure,showing the therapeutic agent perfusion/aspiration/guidewire/pressuresensor hub in a plane perpendicular to the balloon inflation hub.

FIG. 14 depicts detail 14, as indicated in FIG. 13, and shows the distalend of the pressure sensing means, located at the therapeutic agentdelivery segment.

FIG. 15 is a plan view of the catheter assembly of the presentdisclosure, showing the therapeutic agentperfusion/aspiration/guidewire/pressure sensor hub in a planeperpendicular to the balloon inflation hub, and showing the pressuresensor connector.

FIG. 16 is a plan view of the catheter assembly of the presentdisclosure, showing three-way stopcock in line with aspiration port oftherapeutic agent perfusion/aspiration/guidewire hub.

FIG. 17 is a plan view of the catheter assembly of the presentdisclosure, showing three-way stopcock in line with aspiration port oftherapeutic agent perfusion/aspiration/guidewire/pressure sensor hub.

FIG. 18 is a cross-sectional side view of therapeutic agentperfusion/aspiration/guidewire/pressure sensor hub of the presentdisclosure, taken along the line J-J, as shown in FIG. 13. For the sakeof clarity, the balloon inflation hub is not shown in this FIG. 18.

FIG. 19A shows a side elevational view of one embodiment of a catheterof the present disclosure. For clarity, the entire device has not beenshown and the figure is not drawn to scale. FIG. 19B shows across-sectional side view of the balloon inflation/visualization hub ofthe present disclosure, taken along the line N-N, as shown in FIG. 19A.For the sake of clarity, the therapeutic agent perfusion/aspiration andguidewire hub is not shown in this FIG. 19B. FIG. 19C shows across-sectional side view of therapeutic agent perfusion/aspiration andguidewire hub of the present disclosure, along the plane of the page, asshown in FIG. 19A. For the sake of clarity, the ballooninflation/visualization hub is not shown in this FIG. 19C.

FIG. 20 is a cross-sectional view taken along line B-B as shown in FIG.19, displaying a distal occluding balloon, five lumens (which may beemployed to inflate and deflate balloons, deliver and remove therapeuticagents or biologic samples, or accommodate a visualization means), and askive port extending through the thickness of the catheter wall suchthat occluding balloon inflation lumen of the catheter is incommunication with the catheter exterior wall for inflating anddeflating the distal occluding balloon.

FIG. 21 is a cross-sectional view taken along line C-C as shown in FIG.19, displaying five lumens (which may be employed to inflate and deflateballoons, deliver and remove therapeutic agents or biologic samples, oraccommodate a visualization means), and an aspiration skive portextending through the thickness of the catheter wall such thataspiration lumen of the catheter is in communication with the catheterexterior wall for aspirating therapeutic agents or fluid samples fromthe lumen of a blood vessel.

FIG. 22 is a cross-sectional view taken along line D-D as shown in FIG.19, displaying a space occupying balloon, five lumens (which may beemployed to inflate and deflate balloons, deliver and remove therapeuticagents, or accommodate a visualization means), visualization means, anda skive port extending through the thickness of the catheter wall suchthat the visualization lumen of the catheter is in communication withthe catheter exterior wall for visualizing the treatment region.

FIG. 23 is a cross-sectional view taken along line E-E as shown in FIG.19, displaying five lumens (which may be employed to inflate and deflateballoons, deliver and remove therapeutic agents, or accommodate avisualization means), a visualization means, and a skive port extendingthrough the thickness of the catheter wall such that therapeutic agentdelivery lumen of the catheter is in communication with the catheterexterior wall for delivering therapeutic agents to the lumen of a bloodvessel.

FIG. 24 is a cross-sectional view taken along line F-F as shown in FIG.19, displaying a proximal occluding balloon, five lumens (which may beemployed to inflate and deflate balloons, deliver and remove therapeuticagents, or accommodate a visualization means), a visualization means,and a skive port extending through the thickness of the catheter wallsuch that occluding balloon inflation lumen of the catheter is incommunication with the catheter exterior wall for inflating anddeflating the proximal occluding balloon.

FIG. 25 is a perspective view showing the distal portion of a catheterof the present disclosure with the distal and proximal occludingballoons inflated, the visualization means slot between said balloons,and the visualization means exiting the visualization means slot.

FIG. 26 depicts detail 26, as indicated in FIG. 25, and shows thevisualization means exiting the visualization means slot.

FIG. 27 is a perspective view showing the distal portion of a catheterof the present disclosure with the distal and proximal occludingballoons inflated, the visualization means slot between said balloons,and the visualization means more fully outside the visualization meansslot.

FIG. 28 depicts detail 28, as indicated in FIG. 27, and shows thevisualization means more fully outside the visualization means slot.

FIG. 29 is a perspective view of a catheter of the present invention,showing the visualization means attachment to the proximal end adapter.

FIG. 30 depicts detail 30, as indicated in FIG. 29, and shows thevisualization means attachment to the proximal end adapter.

DETAILED DESCRIPTION

Before the catheter of the present disclosure is further described, itis to be understood that the disclosure is not limited to the particularembodiments described below, as variations of the particular embodimentsmay be made and still fall within the scope of the appended claims. Itis also to be understood that the terminology employed is for thepurpose of describing particular embodiments, and is not intended to belimiting. Instead, the scope of the present disclosure will beestablished by the appended claims.

In this specification and the appended claims, the singular forms “a,”“an,” and “the” include plural reference unless the context clearlydictates otherwise. Unless defined otherwise, all technical andscientific terms used herein have the same meaning as commonlyunderstood to one of ordinary skill in the art to which this disclosurebelongs.

As used herein, the term “skive” or “skive port” is synonymous with“orifice.”

As illustrated in FIGS. 1, 2, 12A and 12B, one embodiment of thecatheter assembly (100) comprises a catheter (150) extending from aproximal end adapter (110) and longitudinally movable within a vessel(10) (see FIGS. 12A and 12B) along the catheter longitudinal axis (170).Catheter (150) includes elongate catheter shaft (160) havinglongitudinal axis (170) and defining five lumens therein. At its distalend (140), the catheter assembly (100) has an atraumatic tapered distaltip (200). A distal occluding balloon (210) is located proximal to thetapered distal tip (200) along the longitudinal axis (170) of thecatheter (150), a space-occupying balloon (230) is located proximal tothe distal occluding balloon (210) along the longitudinal axis (170) ofthe catheter (150), and a proximal occluding balloon (250) is locatedproximal to the space-occupying balloon (230) along the longitudinalaxis (170) of the catheter (150). Between the distal occluding balloon(210) and the space-occupying balloon (230) is an aspiration segment(220), and between the space-occupying balloon (230) and the proximaloccluding balloon (250) is located an agent delivery segment (240). Eachof the aspiration segment (220) and the agent delivery segment (240)have at least one skive port (420 and 440, respectively) formed therein(see also: FIGS. 12A and 12B). Proximal end adapter (110) includesoccluding balloon inflation hub (120) and delivery hub (130).

As seen in FIGS. 1, 2, and 9, occluding balloon inflation hub (120)comprises distal and proximal occluding balloon inflation port (510) andspace-occupying balloon inflation port (530). Distal and proximaloccluding balloon inflation port (510) communicates with distal andproximal occluding balloon inflation lumen (310) via skive port (610),and permits distal and proximal occluding balloons (210 and 250,respectively), discussed below, to be inflated and deflated—intandem—during use. Space-occupying balloon inflation port (530)communicates with space occupying balloon inflation lumen (330) viaskive port (630), and permits space-occupying balloon (230), discussedbelow, to be inflated and deflated—independently of the distal andproximal occluding balloons—during use.

As seen in FIGS. 1, 2, and 11, therapeutic agent perfusion/aspirationand guidewire hub (the “perfusion/aspiration hub,” 130) comprisestherapeutic agent delivery port (540), therapeutic agent aspiration port(520), and guidewire port (500). Therapeutic agent delivery port (540)communicates with therapeutic agent delivery lumen (340) via skive port(640), and permits delivery of therapeutic agent via skive port (440) tothe lumen (18) of a blood vessel (10). Therapeutic agent aspiration port(520) communicates with aspiration lumen (320) via skive port (620), andpermits aspiration of therapeutic agents or fluid samples via skive port(420) from the lumen (18) of a blood vessel (10) (see, e.g., FIG. 12B).Guidewire port (500) is in communication with guidewire lumen (300),which extends the entire length of the catheter (150) to emerge atatraumatic tapered tip (200) as distal opening (202), and permits“over-the-wire” use. As will be appreciated by those of ordinary skillin the art, and as indicated by the jagged line breaks in FIGS. 1, 2, 8,10, 12A, 12B, 13, and 15-18, the catheter (100) may be either longer orshorter so that the distal end (140) may reach the desired locationwithin a patient while the proximal end adapter (110) remains outsidethe patient. Between therapeutic agent perfusion/aspiration andguidewire hub (130) and occluding balloon inflation hub (120), thecatheter (180) possesses three lumens (300, 320, 340).

Referring now to FIGS. 1-3, 9, and 11, FIG. 3 is a cross-sectional viewof the catheter of FIG. 1 taken along line B-B, and illustrates: distaloccluding balloon (210); guidewire lumen (300), which communicates withguidewire port (500); distal and proximal occluding balloon inflationlumen (310), which communicates with occlusion balloon inflation port(510) via skive port (610); space occupying balloon inflation lumen(330), which communicates with space-occupying balloon inflation port(530) via skive port (630); aspiration lumen (320), which communicateswith aspiration port (520) via skive port (620); therapeutic agentdelivery lumen (340), which communicates with drug delivery port (540)via skive port (640); and distal occluding balloon inflation skive port(410). Distal occluding balloon inflation skive port (410) extendsthrough the thickness of the catheter exterior wall (380) such thatoccluding balloon inflation lumen (310) of the catheter (150) is incommunication with the catheter exterior wall (380) for inflating thedistal occluding balloon (210).

Referring now to FIGS. 1, 2, 4, 9, and 11, FIG. 4 is a cross-sectionalview of the catheter of FIG. 1 taken along line C-C, and illustrates across-sectional view of the therapeutic agent aspiration segment (220).Referring now to FIGS. 1, 2, 4, 9, and 11, FIG. 4 shows: guidewire lumen(300), which communicates with guidewire port (500); distal and proximaloccluding balloon inflation lumen (310), which communicates withocclusion balloon inflation port (510) via skive port (610); spaceoccupying balloon inflation lumen (330), which communicates withspace-occupying balloon inflation port (530) via skive port (630);aspiration lumen (320), which communicates with aspiration port (520)via skive port (620); therapeutic agent delivery lumen (340), whichcommunicates with perfusion port (540) via skive port (640); andaspiration skive port (420). Aspiration skive port (420) extends throughthe thickness of the catheter exterior wall (380) such that aspirationlumen (320) of the catheter (150) is in communication with the catheterexterior wall (380) for aspirating therapeutic agents or liquid samplesfrom the lumen (18) of a blood vessel (10) (see, e.g., FIGS. 12A and12B).

Referring now to FIGS. 1, 2, 5, 9, and 11, FIG. 5 is a cross-sectionalview of the catheter of FIG. 1 taken along line D-D, and illustrates:space-occupying balloon (230); guidewire lumen (300), which communicateswith guidewire port (500); distal and proximal occluding ballooninflation lumen (310), which communicates with occlusion ballooninflation port (510) via skive port (610); space occupying ballooninflation lumen (330), which communicates with space-occupying ballooninflation port (530) via skive port (630); aspiration lumen (320), whichcommunicates with aspiration port (520) via skive port (620);therapeutic agent delivery lumen (340), which communicates with drugdelivery port (540) via skive port (640); and space-occupying ballooninflation skive port (430). Space-occupying balloon inflation skive port(430) extends through the thickness of the catheter exterior wall (380)such that space-occupying balloon inflation lumen (330) of the catheter(150) is in communication with the catheter exterior wall (380) forinflating and deflating the space occupying balloon (230).

FIG. 6 is a cross-sectional view of the catheter of FIG. 1 taken alongline E-E, and illustrates a cross-sectional view of the therapeuticagent delivery segment (240). Referring now to FIGS. 1, 2, 6, 9, and 11,FIG. 6 shows: guidewire lumen (300), which communicates with guidewireport (500); distal and proximal occluding balloon inflation lumen (310),which communicates with occlusion balloon inflation port (510) via skiveport (610); space occupying balloon inflation lumen (330), whichcommunicates with space-occupying balloon inflation port (530) via skiveport (630); aspiration lumen (320), which communicates with aspirationport (520) via skive port (620); therapeutic agent delivery lumen (340),which communicates with perfusion port (540) via skive port (640); anddrug delivery skive port (440). Drug delivery skive port (440) extendsthrough the thickness of the catheter exterior wall (380) such that drugdelivery lumen (340) of the catheter (150) is in communication with thecatheter exterior wall (380) for delivering therapeutic agents to thelumen (18) of a blood vessel (10) (see, e.g., FIGS. 12A and 12B).

Referring now to FIGS. 1, 2, 7, 9, and 11, FIG. 7 is a cross-sectionalview of the catheter of FIG. 1 taken along line F-F. FIG. 7 illustrates:proximal occluding balloon (250); guidewire lumen (300), whichcommunicates with guidewire port (500); distal and proximal occludingballoon inflation lumen (310), which communicates with occlusion ballooninflation port (510) via skive port (610); space occupying ballooninflation lumen (330), which communicates with space-occupying ballooninflation port (530) via skive port (630); aspiration lumen (320), whichcommunicates with aspiration port (520) via skive port (620);therapeutic agent delivery lumen (340), which communicates with drugdelivery port (540) via skive port (640); and proximal occluding ballooninflation skive port (450). Proximal occluding balloon inflation skiveport (450) extends through the thickness of the catheter exterior wall(380) such that occluding balloon inflation lumen (310) of the catheter(150) is in communication with the catheter exterior wall (380) forinflating the proximal occluding balloon (250).

Referring to FIGS. 3-7, the catheter (160) has a catheter exterior wall(380) and a catheter interior wall (390). As may be appreciated fromFIGS. 2, 3-7, 9, and 11, the catheter interior wall (390) defines theguide wire lumen (300). Lumens (330, 340, 310, 320) are peripheral toguidewire lumen (300); they are formed within the catheter (150) andlocated between the catheter interior wall (390) and the catheterexterior wall (380). The five lumens (300, 310, 340, 330, 320) extendlongitudinally through the catheter (150), interconnecting the openproximal end (500, 510, 540, 530, and 520, respectively) with the opendistal end (202, 410/450, 440, 430, and 420, respectively).

As seen in FIGS. 8 and 9, balloon inflation hub (120) is a component ofthe proximal end adapter (110), lying proximal to the distal end (140)and distal to the therapeutic agent perfusion/aspiration and guidewirehub (130). It will be appreciated by those of ordinary skill in the artthat the positions of the balloon inflation hub (120) and thetherapeutic agent perfusion/aspiration and guidewire hub (130) may bereversed with respect to one another so that the therapeutic agentperfusion/aspiration and guidewire hub (130) lies between the distal end(140) and the balloon inflation hub (120).

The balloon inflation hub (120) is comprised of occlusion ballooninflation port (510), space occupying balloon inflation port (530), andcatheter shaft (160). Occlusion balloon inflation port (510) iscommunicably connected to occlusion balloon inflation lumen (310) ofcatheter shaft (160) via occlusion balloons hub inflation skive (610).Space occupying balloon inflation port (530) is communicably connectedto space occupying balloon inflation lumen (330) of catheter shaft (160)via space occupying balloon hub inflation skive (630).

As seen in FIGS. 10 and 11, therapeutic agent perfusion/aspiration andguidewire hub (130) is a component of the proximal end adapter (110),lying proximal to the distal end (140) and proximal to the ballooninflation hub (120). The therapeutic agent perfusion/aspiration andguidewire hub (130) is comprised of therapeutic agent perfusion port(540), aspiration port (520), guidewire port (500), and catheter shaft(160). Therapeutic agent perfusion port (540) is communicably connectedto therapeutic agent perfusion lumen (340) of catheter shaft (160) viaperfusion hub skive (640). Aspiration port (520) is communicablyconnected to aspiration lumen (320) of catheter shaft (160) viaaspiration hub skive (620). Guidewire port (500) is communicablyconnected to guidewire lumen (300), which encloses the longitudinal axis(170) of the OPC (100). In the present embodiment, and as shown in FIGS.3-7, the longitudinal axis (170) is centered within the circularcross-section of the guidewire lumen (300).

FIGS. 12A and 12B show the distal and proximal occlusion balloons (210,250) as they would appear when inflated inside a vessel (10) or otherhollow body structure. It will be appreciated by those of ordinary skillin the art that occluding balloons (210, 250), space-occupying balloon(230), catheter (150, 160), and other components of the device of thepresent disclosure (100) may be sized appropriately to account for thedimensions that would be required in other hollow body structures (forexample, but without intending to be limited, vessels of the lymphaticsystem, the gastroesophageal tract, the portal-caval system of theliver, the gall bladder and bile ducts, the urinary system, therespiratory system, ducts of the endocrine and exocrine organs, andreproductive organs). FIGS. 12A and 12B show space-occupying balloon(230) as it would appear before inflation and after inflation,respectively. Referring to FIGS. 2, 12A, and 12B, distal and proximalradio-opaque marker bands (260, 270, respectively) are also shownlocated on the “shoulders” of the space-occupying balloon (230) tofacilitate visualization, under fluoroscopic imaging, of the catheter(150) within a vessel (10). It will be appreciated by those of ordinaryskill in the art that radio-opaque markers may also be located upon thecatheter shaft (for example, and without limitation, along theaspiration segment (220) or the therapeutic agent delivery segment(240). More preferably, one of the marker bands is located on the shaft(150) at the most distal portion of the aspiration segment (220), and asecond marker band is located on the shaft (150) at the most proximalportion of the therapeutic agent delivery segment (240). Alternatively,one of the marker bands is located on the shaft (150) at or near distalocclusion balloon inflation skive (FIG. 3, 410), and a second markerband is located on the shaft (150) at or near proximal occluding ballooninflation skive (FIG. 7, 450). In either of these embodiments, the gapbetween the two radio-opaque marker bands aids in approximating thetreatment volume and treatment location. It will also be appreciatedthat one marker band may be used, instead of a plurality. The markerbands (260, 270) may optionally be rotationally specific (e.g., having agenerally “U-shaped” configuration) so that the rotational position ofthe distal end (140) of the catheter (150) will be apparent when themarkers are observed in a two-dimensional fluoroscopic image.Alternatively, contrast fluid may be used to inflate any one or all ofthe balloons (210, 230, and/or 250), or may be injected through drugdelivery skive port (440) or through guidewire lumen (300) to emerge atthe distal tapered tip (200) from the opening (202).

As seen in FIG. 12A, the inflation of distal and proximal occlusionballoons (210, 250) inside the lumen (20) of a blood vessel (10),without inflation of space-occupying balloon (230), leads to theircontact with vessel endothelium (50) and occlusion of a comparativelylarge intraluminal space (30). Subsequent inflation of the spaceoccupying balloon (230), as shown in FIG. 12B, reduces the intraluminalvolume exterior to the balloons to produce occlusion of a comparativelysmall intraluminal space (40), and thus reduces the treatment volume ofthe targeted vessel segment (60). By “treatment volume” is meant thevolume of the vessel, between the expanded occlusion balloons (210,250), minus the volume of the space-occupying balloon (230).Consequently, deflation of the space-occupying balloon leads toincreased treatment volume while inflation of the space-occupyingballoon reduces the treatment volume. As can be seen in FIG. 12B, fluidcommunication between therapeutic agent delivery segment (240) andaspiration segment (220) is maintained (40) despite inflation ofspace-occupying balloon (230) because the balloon (230) is not incontact with vessel endothelium (50).

As shown in FIGS. 3-7, the longitudinal axis (170) is contained withinthe guide wire lumen (300), but persons having ordinary skill in the artwill recognize that the arrangement of lumens may be altered to offsetthe central lumen (300) from the longitudinal axis (170). Lumens (330,340, 310, and 320) are formed within the catheter (150) and are locatedsubstantially between the catheter exterior wall (380) and the catheterinterior wall (390). The lumens (300, 330, 340, 310, and 320) extendlongitudinally through the catheter (150), but only guidewire lumen(300) is patent along the entire length of the catheter (150), emergingat the distal tapered tip (200) as opening (202) and so allowing“over-the-wire” use.

Inflation of the distal occluding balloon (210) and the proximaloccluding balloon (250) creates a substantially cylindrical deliveryregion bounded distally and proximally by the inflated distal andproximal occluding balloons (210 and 250, respectively) and boundedcircumferentially by vessel (10), as shown in FIG. 12A. Distal andproximal occluding balloons (210 and 250, respectively) are constructedof a compliant to semi-compliant material (e.g., without limitation,polyethylene terephthalate, nylon, polyurethane, or other thermoplasticpolymers), which means that they retain their shape as they generateforce and form a seal against blood flow without imparting excessivepressure to the blood vessel. With only the distal and proximaloccluding balloons (210 and 250, respectively) inflated and thespace-filling balloon (230) deflated, though, a relatively largetreatment volume remains within the occluded vessel lumen (30), as shownin FIG. 12A. This large volume is particularly undesirable when scarceor expensive agents are delivered; it is potentially harmful when toxicagents are to be delivered because a greater volume of those agents isrequired. The greater treatment volume thus produces increased expenseand risk.

Inflation of the space-occupying balloon (230) dramatically reduces thespace remaining within the occluded vessel lumen (40), as shown in FIG.12B, thereby increasing the effective application of agent deliveredwhile simultaneously reducing the amount of agent needed. The spaceoccupying balloon (230) is constructed of a non-compliant tosemi-compliant material (e.g., without limitation, polyurethane, nylonelastomers, polyethylene terephthalate, or other thermoplasticpolymers). The space-occupying balloon (230) is inflated to a degreethat it does not contact the vessel endothelium (50), thus leaving theentire region of endothelium (50) between the inflated distal andproximal occluding balloons (210 and 250, respectively) available forexposure to the delivered agent.

In one embodiment, the guide wire lumen (300) provides access to aguidewire (not shown), via distal opening (202) in atraumatic taperedtip (200), while distal and proximal occluding balloon inflation lumen(310) and space-occupying balloon inflation lumen (330) provide accessfor balloon inflation ports (510 and 530, respectively) for the distal(210) and proximal (250) occluding balloons and for the space-occupyingballoon (230), respectively. Agent delivery port (540) is incommunication with agent delivery lumen (340) via skive port (640), andagent delivery lumen (340) is also in communication with vessel lumen(18) via skive port (440) at agent delivery segment (240), for thedelivery of therapeutic agents to the occluded vessel lumen (18, 30,40). Aspiration port (520) is in communication with aspiration lumen(320) via skive port (620), and aspiration lumen (320) is incommunication with vessel lumen (18) via skive port (420) at aspirationsegment (220), for aspiration of agents or other fluid samples from thevessel lumen (18, 30, 40). In one aspect of this embodiment, there maybe provided a two- or three-way valve or check valve (710) in fluidcommunication with the agent delivery lumen (340), the aspiration lumen(320, as shown in FIGS. 16 and 17), or both, to prevent injection viathe aspiration lumen (320), aspiration or backflow via the agentdelivery lumen (340), or both (respectively).

In another aspect of this embodiment, the catheter (100) may include afirst pressure sensing means (700), as seen in FIGS. 13-15 and 18,incorporated into the catheter shaft (190, 192) and hub (130 a) of theadapter (110). Without intending to be limited thereby, an example of asuitable pressure sensing means (700) is the FOP-MIV (SequoiaTechnology, Ltd.; Reading, UK)—a fiber optic pressure sensor. Suchpressure sensing means has a distal end (702), a proximal end (701)located at pressure sensor connector (550), and a length therebetween.Via pressure sensor connector (550), which is in fluid communicationwith therapeutic agent perfusion lumen (340), the pressure sensing meansenters therapeutic agent perfusion lumen (340) and extends to a positionat or near perfusion/delivery skive (440) at therapeutic agent deliverysegment (240), as shown in FIG. 14. Via skive (440), therapeutic agentdelivery lumen (340) of the catheter (150) is in communication with thecatheter exterior wall (380) for delivering therapeutic agents to thelumen (18, 30, 40) of a blood vessel (10), as seen in FIGS. 12A and 12B.Thus, the pressure sensing means distal end (702) is in communicationwith the treatment region (60). In this aspect of the catheter (100) ofthe present disclosure, there may be provided a two- or three-way valveor check valve (710) in line with the agent delivery lumen (340), theaspiration lumen (320, via aspiration port (520), as shown in FIGS.16-17), or both, to prevent injection via the aspiration lumen (320),aspiration or backflow via the agent delivery lumen (340), or both(respectively). For the sake of clarity, and to reduce redundancy, thetwo- or three-way valve or check valve (710) is shown attached to theaspiration port (520). It will be appreciated by those of ordinary skillin the art that such a valve (710) or a plurality thereof may beincorporated to any of the ports (500, 510, 520, 530, 540). As will beappreciated by those of ordinary skill in the art, the catheter (100)may also be constructed so that first pressure sensing means (700)occupies its own separate and dedicated lumen within the catheter (150),and having a proximal opening at pressure sensor connector (550) anddistal opening at or near perfusion/delivery skive (440). Betweentherapeutic agent perfusion/aspiration/guidewire/pressure sensor hub(130 a) and occluding balloon inflation hub (120), as indicated by FIGS.15 and 18, the catheter (190) possesses three lumens (300, 320, 340),but may possess a dedicated lumen to house the first pressure sensor(700).

In a related aspect of this embodiment, as shown in FIG. 18, thecatheter (100) of the present disclosure may further comprise a secondpressure sensing means (704) incorporated into the catheter shaft (190,192) and hub (130 a) of the adapter (110), whereby the pressure of thefluid environment within the therapeutic agent perfusion lumen (340)—ator near the perfusion skive (640), or at any point within thetherapeutic agent perfusion lumen (340)—can be known or estimated. Inthis aspect, the second pressure sensing means (704) may be locatedalongside the proximal end of the first pressure sensing means (700),with the second pressure sensing means proximal end (705) also locatedat the pressure sensor connector (550), but with its distal end (706)located within the therapeutic agent perfusion lumen (340) at or nearthe perfusion skive (640), or at any point within the therapeutic agentperfusion lumen (340). Without intending to be bound to a particularpressure sensor, an example of a pressure sensor suitable for thisembodiment is the FOP-MIV (Sequoia Technology, Ltd.; Reading, UK)—afiber optic pressure sensor. Via the second pressure sensing means(704), a user of the device (100) can know or estimate the pressureexperienced by a therapeutic agent at or near the perfusion skive (640).Such information may be particularly relevant for the delivery of suchagents as live cell suspensions or other materials that may besusceptible to pressure and/or shear stress. In this embodiment, and asexplained above for the example with a first pressure sensing means(700), there may be provided a two- or three-way valve or check valve(710) in line with the agent delivery lumen (340), the aspiration lumen(320, via aspiration port (520), as shown in FIGS. 16-17), or both, toprevent injection via the aspiration lumen (320), aspiration or backflowvia the agent delivery lumen (340), or both (respectively).

As illustrated in FIGS. 19A-C, and 25-30, an embodiment of the catheterassembly (105) comprises a catheter (150) extending from a proximal endadapter (110) and longitudinally movable within a vessel (10) along thecatheter longitudinal axis (170). Catheter (150) includes elongatecatheter shaft (160) having longitudinal axis (170) and defining fivelumens therein. At its distal end (140), the catheter assembly (105) hasan atraumatic tapered distal tip (200). A distal occluding balloon (210)is located proximal to the tapered distal tip (200) along thelongitudinal axis (170) of the catheter (150), a visualization meansslot (435) is located proximal to the distal occluding balloon (210)along the longitudinal axis (170) of the catheter (150), and a proximaloccluding balloon (250) is located proximal to the visualization meansslot (435) along the longitudinal axis (170) of the catheter (150).Between the distal occluding balloon (210) and the visualization meansslot (435) is an aspiration segment (220), and between the visualizationmeans slot (435) and the proximal occluding balloon (250) is located anagent delivery segment (240). Each of the aspiration segment (220) andthe agent delivery segment (240) have at least one skive port (420 and440, respectively) formed therein (see also FIGS. 12A and 12B). Proximalend adapter (110) includes balloon inflation/visualization &illumination means hub (125) and delivery hub (130).

As seen in FIGS. 19A-C, 20-24, and 30, balloon inflation/visualization &illumination means hub (125) comprises distal and proximal occludingballoon inflation port (510) and visualization means port (535) (see,e.g., FIG. 19B). Distal and proximal occluding balloon inflation port(510) communicates with distal and proximal occluding balloon inflationlumen (310) via skive port (610), and permits distal and proximaloccluding balloons (210 and 250, respectively), discussed below, to beinflated and deflated—in tandem—during use. Visualization means port(535) communicates with visualization means lumen (335) via skive port(635), and permits the visualization means (235), discussed below, topass through the visualization means lumen (335) to reach and emergefrom the visualization means slot (435). The visualization means port(535) may further comprise a valve (710) (e.g., a Tuohy Borst adapter, atwo-way, three-way, or check valve, etc.) to prevent backflow via thevisualization means lumen (335). The visualization means (235) furthercomprises output (238), whereby the visualization means (235) may conveyinformation (e.g., to a monitor, a computer, etc.), which may bevisualized and/or recorded by means readily available and known in theart.

As seen in FIGS. 19A-C, 20-24, and 30, therapeutic agentperfusion/aspiration and guidewire hub (the “perfusion/aspiration hub,”130) comprises therapeutic agent delivery port (540), therapeutic agentaspiration port (520), and guidewire port (500) (see, e.g., FIG. 19C).Therapeutic agent delivery port (540) communicates with therapeuticagent delivery lumen (340) via skive port (640), and permits delivery oftherapeutic agent via skive port (440) to the lumen (18) of a bloodvessel (10) (see, e.g., FIGS. 12A & 12B). Therapeutic agent aspirationport (520) communicates with aspiration lumen (320) via skive port(620), and permits aspiration of therapeutic agents or fluid samples viaskive port (420) from the lumen (18) of a blood vessel (10) (see, e.g.,FIGS. 12A & 12B). Guidewire port (500) is in communication withguidewire lumen (300), which extends the entire length of the catheter(150) to emerge at atraumatic tapered tip (200) as distal opening (202),and permits “over-the-wire” use. As will be appreciated by those ofordinary skill in the art, and as indicated by the jagged line breaks inFIG. 19, the catheter (105) may be either longer or shorter so that thedistal end (140) may reach the desired location within a patient whilethe proximal end adapter (110) remains outside the patient. Betweentherapeutic agent perfusion/aspiration and guidewire hub (130) andballoon inflation/visualization & illumination means hub (125), thecatheter (180) possesses three lumens (300, 320, 340).

Referring now to FIGS. 19A-C, 20, and 25-28, FIG. 20 is across-sectional view of the catheter of FIG. 19 taken along line I-I,and illustrates: distal occluding balloon (210); guidewire lumen (300),which communicates with guidewire port (500); distal and proximaloccluding balloon inflation lumen (310), which communicates withocclusion balloon inflation port (510) via skive port (610);visualization means lumen (335), which communicates with visualizationmeans port (535) via skive port (635); aspiration lumen (320), whichcommunicates with aspiration port (520) via skive port (620);therapeutic agent delivery lumen (340), which communicates with drugdelivery port (540) via skive port (640); and distal occluding ballooninflation skive port (410). Distal occluding balloon inflation skiveport (410) extends through the thickness of the catheter exterior wall(380) such that occluding balloon inflation lumen (310) of the catheter(150) is in communication with the catheter exterior wall (380) forinflating the distal occluding balloon (210).

Referring now to FIGS. 19A-C, 21, and 25-28, FIG. 21 is across-sectional view of the catheter of FIG. 19 taken along line J-J,and illustrates a cross-sectional view of the therapeutic agentaspiration segment (220), showing: guidewire lumen (300), whichcommunicates with guidewire port (500); distal and proximal occludingballoon inflation lumen (310), which communicates with occlusion ballooninflation port (510) via skive port (610); visualization means lumen(335), which communicates with visualization means port (535) via skiveport (635); aspiration lumen (320), which communicates with aspirationport (520) via skive port (620); therapeutic agent delivery lumen (340),which communicates with perfusion port (540) via skive port (640); andaspiration skive port (420). Aspiration skive port (420) extends throughthe thickness of the catheter exterior wall (380) such that aspirationlumen (320) of the catheter (150) is in communication with the catheterexterior wall (380) for aspirating therapeutic agents or liquid samplesfrom the lumen (18) of a blood vessel (10) (see, e.g., FIGS. 12A and12B).

Referring now to FIGS. 19A-C, 22, and 25-28, FIG. 22 is across-sectional view of the catheter of FIG. 19 taken along line K-K,and illustrates: guidewire lumen (300), which communicates withguidewire port (500); distal and proximal occluding balloon inflationlumen (310), which communicates with occlusion balloon inflation port(510) via skive port (610); visualization means (235) contained withinvisualization means lumen (335), which communicates with visualizationmeans port (535) via skive port (635); aspiration lumen (320), whichcommunicates with aspiration port (520) via skive port (620);therapeutic agent delivery lumen (340), which communicates with drugdelivery port (540) via skive port (640); and space-occupying ballooninflation skive port (430). Visualization means slot (435) extendsthrough the thickness of the catheter exterior wall (380) such thatvisualization means lumen (335) of the catheter (150) is incommunication with the catheter exterior wall (380) for allowing thevisualization means (235) to exit the visualization means slot (435) andlumen (335) and enter the lumen (18) of a blood vessel (10).Visualization means slot (435) extends parallel to the longitudinal axis(170) and between aspiration segment (220) and therapeutic agentdelivery segment (240) for a length sufficient to allow thevisualization means (235) to exit the visualization means slot (435), asshown in FIGS. 27 and 28. By exiting the visualization means slot (435),the visualization means (235) enables visualization of the vessel lumenin a 360° radius (that is, all of the vessel inner wall, without theview being obstructed by the catheter itself).

Referring now to FIGS. 19A-C, 23, and 25-28, FIG. 23 is across-sectional view of the catheter of FIG. 19 taken along line L-L,and shows: guidewire lumen (300), which communicates with guidewire port(500); distal and proximal occluding balloon inflation lumen (310),which communicates with occlusion balloon inflation port (510) via skiveport (610); visualization means (235) contained within visualizationmeans lumen (335), which communicates with visualization means port(535) via skive port (635); aspiration lumen (320), which communicateswith aspiration port (520) via skive port (620); therapeutic agentdelivery lumen (340), which communicates with perfusion port (540) viaskive port (640); and drug delivery skive port (440). Drug deliveryskive port (440) extends through the thickness of the catheter exteriorwall (380) such that drug delivery lumen (340) of the catheter (150) isin communication with the catheter exterior wall (380) for deliveringtherapeutic agents to the lumen (18) of a blood vessel (10) (see, e.g.,FIGS. 12A and 12B).

Referring now to FIGS. 19A-C, 24, and 25-28, FIG. 24 is across-sectional view of the catheter of FIG. 19 taken along line M-M,and shows: proximal occluding balloon (250); guidewire lumen (300),which communicates with guidewire port (500); distal and proximaloccluding balloon inflation lumen (310), which communicates withocclusion balloon inflation port (510) via skive port (610);visualization means (235) contained within visualization means lumen(335), which communicates with visualization means port (535) via skiveport (635); aspiration lumen (320), which communicates with aspirationport (520) via skive port (620); therapeutic agent delivery lumen (340),which communicates with drug delivery port (540) via skive port (640);and proximal occluding balloon inflation skive port (450). Proximaloccluding balloon inflation skive port (450) extends through thethickness of the catheter exterior wall (380) such that occludingballoon inflation lumen (310) of the catheter (150) is in communicationwith the catheter exterior wall (380) for inflating the proximaloccluding balloon (250).

Referring to FIGS. 20-24, the catheter (160) has a catheter exteriorwall (380) and a catheter interior wall (390). As may be appreciatedfrom FIGS. 19A-C, and 20-28, the catheter interior wall (390) definesthe guide wire lumen (300). Lumens (335, 340, 310, 320) are peripheralto guidewire lumen (300); they are formed within the catheter (150) andlocated between the catheter interior wall (390) and the catheterexterior wall (380). The five lumens (300, 310, 340, 335, 320) extendlongitudinally through the catheter (150), interconnecting the openproximal end (500, 510, 540, 535, and 520, respectively) with the opendistal end (202, 410/450, 440, 435, and 420, respectively).

As seen in FIGS. 19A and 19B, balloon inflation/visualization &illumination means hub (125) is a component of the proximal end adapter(110), lying proximal to the distal end (140) and distal to thetherapeutic agent perfusion/aspiration and guidewire hub (130). It willbe appreciated by those of ordinary skill in the art that the positionsof the balloon inflation/visualization & illumination means hub (125)and the therapeutic agent perfusion/aspiration and guidewire hub (130)may be reversed with respect to one another so that the therapeuticagent perfusion/aspiration and guidewire hub (130) lies between thedistal end (140) and the balloon inflation/visualization & illuminationmeans hub (125). The balloon inflation/visualization & illuminationmeans hub (125) is comprised of occlusion balloon inflation port (510),visualization means port (535), and catheter shaft (160). Occlusionballoon inflation port (510) is communicably connected to occlusionballoon inflation lumen (310) of catheter shaft (160) via occlusionballoons hub inflation skive (610). Visualization means port (535) iscommunicably connected to visualization means lumen (335) of cathetershaft (160) via skive port (635).

As seen in FIGS. 19A and 19C, therapeutic agent perfusion/aspiration andguidewire hub (130) is a component of the proximal end adapter (110),lying proximal to the distal end (140) and proximal to the ballooninflation/visualization & illumination means hub (125). The therapeuticagent perfusion/aspiration and guidewire hub (130) is comprised oftherapeutic agent perfusion port (540), aspiration port (520), guidewireport (500), and catheter shaft (160). Therapeutic agent perfusion port(540) is communicably connected to therapeutic agent perfusion lumen(340) of catheter shaft (160) via perfusion hub skive (640). Aspirationport (520) is communicably connected to aspiration lumen (320) ofcatheter shaft (160) via aspiration hub skive (620). Guidewire port(500) is communicably connected to guidewire lumen (300), which enclosesthe longitudinal axis (170) of the OVC (105). In the present embodiment,and as shown in FIGS. 20-24, the longitudinal axis (170) is centeredwithin the circular cross-section of the guidewire lumen (300).

FIGS. 25-28 and 12B show the distal and proximal occlusion balloons(210, 250) as they would appear when inflated inside a vessel (10) orother hollow body structure, and show the visualization means (235) asit would appear as it exits the visualization means slot (435). It willbe appreciated by those of ordinary skill in the art that occludingballoons (210, 250), visualization means (235), catheter (150, 160), andother components of the device of the present disclosure (105) may besized appropriately to account for the dimensions that would be requiredin other hollow body structures (for example, but without intending tobe limited, vessels of the lymphatic system, the gastroesophageal tract,the portal-caval system of the liver, the gall bladder and bile ducts,the urinary system, the respiratory system, ducts of the endocrine andexocrine organs, and reproductive organs). Referring to FIG. 25, distaland proximal radio-opaque marker bands (260, 270, respectively) are alsoshown located on the catheter distal end (140) to facilitatevisualization, under fluoroscopic imaging, of the device (105) within avessel (10). It will be appreciated by those of ordinary skill in theart that radio-opaque markers may also be located upon other portions ofthe device (105), for example, and without limitation, along theaspiration segment (220), the therapeutic agent delivery segment (240),the occlusion balloons (210, 250), and as described above for the OPC(100). Alternatively, contrast fluid may be used to inflate theocclusion balloons (210, 250), or may be injected through drug deliveryskive port (440) or through guidewire lumen (300) to emerge at thedistal tapered tip (200) from the opening (202).

As seen in FIGS. 25 and 26, the visualization means (235) may exit thevisualization means slot (435) at the slot's most proximal end. Thevisualization means (235) may, optionally, comprise a bend at its mostdistal end to facilitate exit from the visualization means lumen (335)and visualization means slot (435). Referring now to FIGS. 27 and 28, asthe visualization means (235) is inserted further distally, along thevisualization means lumen (335), the visualization means (235) mayfurther exit the visualization means lumen (335) via the visualizationmeans slot (435) so that the visualization means (235) distal end liesfurther from the longitudinal axis (170). By allowing the visualizationmeans (235) distal end to depart from the longitudinal axis (170), asshown in FIGS. 27 and 28, and by applying torque to the visualizationmeans (235), the visualization means may turn about the longitudinalaxis (170) and so enables visualization of the entire vessel lumensurrounding the device and between the occluding balloons (210, 250).Inflation of the distal occluding balloon (210) and the proximaloccluding balloon (250) creates a substantially cylindricalvisualization region bounded distally and proximally by the inflateddistal and proximal occluding balloons (210 and 250, respectively) andbounded circumferentially by vessel (10), as shown, for example, in FIG.12A. With only the distal and proximal occluding balloons (210 and 250,respectively) of the device (105) inflated, a relatively large volumeremains within the occluded vessel lumen (30), which may advantageouslybe visualized in its entirety via the visualization means (235).

As shown in FIGS. 20-24, the longitudinal axis (170) is contained withinthe guide wire lumen (300), but persons having ordinary skill in the artwill recognize that the arrangement of lumens may be altered to offsetthe central lumen (300) from the longitudinal axis (170). Lumens (335,340, 310, and 320) are formed within the catheter (150) and are locatedsubstantially between the catheter exterior wall (380) and the catheterinterior wall (390). The lumens (300, 335, 340, 310, and 320) extendlongitudinally through the catheter (150), but only guidewire lumen(300) is patent along the entire length of the catheter (150), emergingat the distal tapered tip (200) as opening (202) and so allowing“over-the-wire” use.

In one aspect of this embodiment the catheter (105) may further compriseone or more two- or three-way valves or check valves (710) in fluidcommunication with the agent delivery lumen (340), the aspiration lumen(320), the visualization means lumen (335) or all three, to preventinjection via the aspiration lumen (320), aspiration or backflow via theagent delivery lumen (340), backflow via the visualization means lumen(335) or all three (respectively). As shown in FIG. 30, a one-way checkvalve (e.g., a Tuohy-Borst adapter, 710) may be used to prevent backflowvia the visualization means lumen (335).

In another aspect of this embodiment, the OVC catheter (105) may includea first pressure sensing means incorporated into the catheter shaft andtherapeutic agent perfusion/aspiration/guide wire hub of the adapter(110), as shown and described above for the OPC (100). Without intendingto be limited thereby, an example of a suitable pressure sensing meansis the FOP-MIV (Sequoia Technology, Ltd.; Reading, UK)—a fiber opticpressure sensor. In a related aspect of this embodiment, the OVCcatheter (105) of the present disclosure may further comprise a secondpressure sensing means incorporated into the catheter shaft andtherapeutic agent perfusion/aspiration/guide wire hub of the adapter(110), as shown and described above for the OPC (100), whereby thepressure of the fluid environment within the therapeutic agent perfusionlumen (340)—at or near the perfusion skive (640), or at any point withinthe therapeutic agent perfusion lumen (340)—can be known or estimated.

In all embodiments, the catheter (100) can be used with a guide wire(not shown), via guide wire lumen (300), to assist in guiding thecatheter (100) to the target segment (60) of the vessel (10). Thecatheter shafts (150) of the present disclosure are preferably betweenabout 2-7 French units (“Fr.” where one French equals ⅓ of a millimeter,or about 0.013 inches). The catheter shafts to be used in coronaryarteries are preferably between about 3-5 Fr. in diameter, and mostpreferably about 3 Fr. The catheter shafts to be used in peripheralvessels are preferably between about 5-8 Fr. in diameter, and mostpreferably 5 Fr.

The catheter shafts can be made of materials including, but not limitedto polymers, natural or synthetic rubber, metal and plastic orcombinations thereof, nylon, Pebax, nylon/Pebax blend, Hytrel® andpolyethylene. The shaft materials can be selected so as to maximizecolumn strength to the longitudinal length of the shaft. Further, theshaft materials can be braided, so as to provide sufficient columnstrength. The shaft materials can also be selected so as to allow thedevice to move smoothly along a guide wire. The catheter (100) can alsobe provided with a lubricious coating as well as antimicrobial andantithrombogenic coatings, as are known to those of skill in the art.The shaft materials can also be selected so as to maximize bonding ofthe shaft to the balloon materials. The shaft materials should beselected so as not to interfere with the efficacy of the agent to bedelivered or collected. This interference may take the form of absorbingthe agent, adhering to the agent or altering the agent in any way, forexample.

The balloons can be made of materials including, but not limited toKraton®, polyurethane, polyolefin or any other biocompatible,elastometric material, or other soft materials. The materials of theballoons may be selected so as to maximize pliability and/or reduce therisk of damage to tissues. The balloon materials should be selected soas not to interfere with the efficacy of the agent to be delivered orcollected. Balloon (210, 230, 250) inflation sources can be syringes incommunication with lumens (310, 330) via proximal ports (510, 530), orother inflation sources known to those of ordinary skill in the art. Thesyringes—individually or separately—may contain contrast media or gas orother fluids known to those skilled in the art to be safe and effectivefor inflating the balloon.

The distal and proximal occlusion balloons (210, 250) used for coronaryarteries are preferably 2 to 4 mm in diameter when inflated. The distaland proximal occlusion balloons (210, 250) used for peripheral vesselsare preferably 5 to 10 mm in diameter when inflated. The distal andproximal occlusion balloons (210, 250) are preferably about 1 to 2 cm inlength, and football-shaped or spherical, or any suitable shape that acompliant to semi-compliant balloon can achieve. The balloons (210, 250)are most preferably about 1 cm long. However, the length and diameter ofthe balloons can be selected so as to minimize tissue damage. The forceexerted against the vessel interior by occlusion balloons (210, 250) issufficiently great enough to hold the catheter (100) in a stationaryposition within the vessel or other hollow body structure and provide anadequate seal to control blood or fluid flow. However, the force is notso great as to damage the interior surface of the vessel or other hollowbody structure.

Preferably, each occlusion balloon (210, 250) is separated from spaceoccupying balloon (230) by about 1 to 10 mm, or more preferably by about1 to 7 mm, or most preferably by about 1 to 3 mm. The distance betweenthe most proximal edge of distal occlusion balloon (210) and the mostdistal edge of space-occupying balloon (230) defines the aspirationsegment (220) length; the distance between the most distal edge ofproximal occlusion balloon (250) and the most proximal edge ofspace-occupying balloon (230) defines the therapeutic agent deliverysegment (240) length. The aspiration and therapeutic agent deliverysegment lengths are preferably about 1 to 10 mm, or more preferablyabout 1 to 7 mm, or most preferably about 1 to 3 mm.

When using a guide wire, whether the catheter (100) is being used in thecoronary arteries or in the peripheral vasculature, the guide wire ispreferably about 0.014 to 0.018 inches in diameter.

Therapeutic agents useful with the device of the present disclosureinclude any one of or a combination of several agents which are gas,liquid, suspensions, emulsions, or solids, which may be delivered orcollected from the vessel for therapeutic or diagnostic purposes.Therapeutic agents include biologically active substances, or substancescapable of eliciting a biological response, including, but not limitedto endogenous substances (growth factors or cytokines, including, butnot limited to basic fibroblast growth factor, acidic fibroblast growthfactor, vascular endothelial growth factor, angiogenic factors), viralvectors, DNA capable of expressing proteins, sustained release polymers,and unmodified or modified cells. Therapeutic agents can includeangiogenic agents which induce the formation of new blood vessels.Therapeutic agents can also include anti-stenosis or anti-restenosisagents which are used to treat the narrowing of blood vessel walls.

The rate of therapeutic agent delivery to the targeted vessel segment(60), as shown in FIGS. 12A and 12B, can be selected so as to minimizetissue damage. The rate of therapeutic agent delivery can depend upon atleast the size of perfusion/delivery skive (440) and the pressure underwhich the agent is passed through the skive (440). The rate oftherapeutic agent delivery can be controlled by, for example, an osmoticpump or an infusion pump attached in line with perfusion port (540),perfusion lumen (340), and perfusion skive (440); use of a perfusionpump is also compatible with a two- or three-way valve or check valveappropriately in line with such an arrangement.

Other target spaces that may be accessed by the catheter (100) includebut are not limited to any other hollow viscera of the body such as: anyof the blood vessels of the cardiovascular system (arteries and veins);vessels of the lymphatic system; the gastroesophageal tract; theportal-caval system of the liver; the gall bladder and bile ducts; theurinary system; the respiratory system; ducts of the endocrine andexocrine organs; and reproductive organs.

The present disclosure also contemplates a method of using balloonocclusion catheters, such as catheter assembly (100), with or without apressure sensing means (700 and/or 704), and with or without a two- orthree-way or check valve (710), for the delivery and/or the collectionof agents from a targeted vessel segment (60) in vivo.

The following examples of use are not intended to be an exhaustive list,as those familiar in the art will know many more sub-categories oftreatment that keep within the spirit of the disclosure of the deviceand the method.

Example 1

General Steps for Using the OPC

The OPC would be delivered to the treatment site via a minimallyinvasive insertion technique, over a guidewire, to the treatment area,and the occlusion balloons (210, 250) inflated to isolate the treatmentregion. Blood and any other fluid trapped between the two inflatedocclusion balloons (210, 250) would be aspirated from the treatmentregion, and the treatment region flushed with saline. The saline wouldthen be aspirated from the treatment region, the space occupying balloonwould be inflated, and the agent would be injected into the treatmentregion. As appropriate, the aspiration lumen could be controlled via theproximal two- or three-way stopcock or check valve to allow the agent toenter the treatment region and prevent the agent from exiting thetreatment region prematurely, and further allow selected fluid pressureswithin the treatment region to be achieved. The space occupying ballooncould be optionally deflated, partially, to allow the injection of moreagent, whereupon the space occupying balloon would be re-inflated toachieve a greater pressure within the treatment area and to force theagent into the media of the vessel wall. After an appropriate treatmenttime, the space occupying balloon would be deflated, the agent would beoptionally aspirated from the treatment region, and the treatment regionoptionally flushed (e.g., with saline). Finally, the occlusion balloonswould be deflated and the OPC could be withdrawn from the treatmentsite.

If the lesion being treated is long, or there are multiple lesionspresent, the OPC can be repositioned and the steps set forth aboverepeated. As will be clear to those of ordinary skill in the art, thesteps set forth herein are susceptible of multiple variations that liewithin the scope of the present disclosure (e.g., the space occupyingballoon need not be deflated and then re-inflated, or one may elect notto flush the treatment region). The space occupying balloon presents atleast two advantages: by taking up space, it decreases the volume ofagent required (which is important, given that such agents are generallyquite expensive); and it is used to increase pressure within thetreatment region, and so push the agent into the media of the vesselwall—the end target of treatment.

Example 2

Simultaneous Perfuse in/Drain Out (Simultaneous Exchange of Fluids inthe Isolated Volume).

The OPC would be delivered to the treatment site via a minimallyinvasive insertion technique, over a guidewire, and the occlusionballoons (210, 250) inflated to isolate the treatment region. The spaceoccupying balloon (230) would be inflated to minimize the treatmentvolume, with the displaced blood draining out through the evacuationlumen (320). Saline could be used as a flushing agent, or thetherapeutic agent could be directly injected in through the perfusionlumen (340), displacing the remainder of the blood. Once the treatmentregion (60) is filled with the therapeutic agent, a stopcock connectedto the device (via the evacuation port (520) would be closed, allowingcontrolled pressure to be built-up in the treatment region with thecontinued injection of therapeutic agent, resulting in perfusion intothe damaged area of the blood vessel/body lumen. Once treatment iscomplete, the stopcock would be opened, and saline would be injected inthrough the perfusion lumen (340), flushing the treatment region. Thespace occupying balloon (230) and the occlusion balloons (210, 250)would then be deflated, allowing movement or removal of the device.

Example 3

Two-Part Polymeric Agent/Gel Treatment.

This modality allows polymerization at the treatment site. The OPC wouldbe delivered to the treatment site via a minimally invasive insertiontechnique, over a guidewire, and the occlusion balloons (210, 250)inflated to isolate the treatment region. The space occupying balloon(230) would be inflated to minimize the treatment volume, with thedisplaced blood draining out through the evacuation lumen (320). Theremainder of the blood is aspirated out through the evacuation lumen(320), creating a vacuum in the treatment region. A stopcock attached tothe evacuation port (520) would be closed, maintaining the vacuum. Oncethe treatment region is under vacuum, a two part polymeric agent wouldbe injected into the treatment region—part “A” goes in one port (theperfusion lumen (340) for example), while part “B” goes in through theother (the evacuation lumen (320) for example) so that polymerizationtakes place in the treatment region. Controlled pressure to be built-upin the treatment region with the continued injection of two-parttherapeutic agent, or increasing the pressure of the space occupyingballoon, resulting in perfusion/treatment into the damaged area of theblood vessel/body lumen. Once treatment is complete, saline could beinjected in through the evacuation lumen (320) while aspiration isfacilitated through the perfusion lumen (340), which due to its largersize, would be more appropriate for removal of a polymerized solution orgel, flushing the treatment region. The space occupying balloon (230)and the occlusion balloons (210, 250) would then be deflated, allowingmovement or removal of the device. This technique may provide analternative to therapies that might be too time-consuming if the polymeris too thick to otherwise inject in through the lumens directly.

Example 4

Simultaneous Perfuse In/Aspirate Out (Simultaneous Exchange of Fluids inthe Treatment Region).

The OPC would be delivered to the treatment site via a minimallyinvasive insertion technique, over a guidewire, and the occlusionballoons (210, 250) inflated to isolate the treatment region. The spaceoccupying balloon (230) would be inflated to minimize the treatmentvolume, with the displaced blood draining out through the evacuationlumen (320). Saline could be used as a flushing agent, or thetherapeutic agent could be directly injected in through the perfusionlumen (340), while the remainder of the blood is simultaneouslyaspirated out through the evacuation lumen (320). Once the treatmentregion is filled with the therapeutic agent, a stopcock connected to thedevice (via the evacuation port (520) would be closed, allowingcontrolled pressure to be built-up in the treatment region with thecontinued injection of therapeutic agent, resulting in perfusion intothe damaged area of the body lumen. Once treatment is complete, thestopcock would be opened, and saline would be injected in through theperfusion lumen (340), while aspiration is facilitated through theevacuation lumen (320), flushing the treatment region. The spaceoccupying balloon (230) and the occlusion balloons (210, 250) would thenbe deflated, allowing movement or removal of the device.

Example 5

Sequential Aspirate Out/Perfuse In (Sequential Exchange of Fluids in theTreatment Region).

The OPC would be delivered to the treatment site via a minimallyinvasive insertion technique, over a guidewire, and the occlusionballoons (210, 250) inflated to isolate the treatment region. The spaceoccupying balloon (230) would be inflated to minimize the treatmentvolume, with the displaced blood draining out through the evacuationlumen (320). The remainder of the blood is aspirated out through theevacuation lumen (320), creating a vacuum in the treatment region. Astopcock attached to the evacuation port (520) would be closed,maintaining the vacuum. Once the treatment region is under vacuum,therapeutic agent would be injected through the perfusion lumen (340),potentially opening up damaged regions in the intimae for more effectivetreatment. Controlled pressure to be built-up in the treatment regionwith the continued injection of therapeutic agent, resulting inperfusion into the damaged area of the blood vessel/body lumen. Oncetreatment is complete, the stopcock would be opened, and saline would beinjected in through the perfusion lumen (340), while aspiration isfacilitated through the evacuation lumen (320), flushing the treatmentregion. The space occupying balloon (230) and the occlusion balloons(210, 250) would then be deflated, allowing movement or removal of thedevice.

Example 6

Perfuse into the treatment region using one of the techniques describedabove and utilize the space occupying balloon to deploy a stent-graft,trapping the agent between the stent-graft & intimae. This techniquewould delay the inflation of the space occupying balloon (230) until thetherapeutic agent has filled the volume of the treatment region.

Example 7

General Steps for Using the OVC

The OVC would be delivered to the treatment site via a minimallyinvasive insertion technique, over a guidewire, to the treatment area,and the occlusion balloons (210, 250) inflated to isolate the treatmentregion. Blood and any other fluid trapped between the two inflatedocclusion balloons (210, 250) would be aspirated from the treatmentregion, and the treatment region flushed with saline. Optionally, salinecould remain within the treatment region to facilitate visualization.The visualization means (235) would be inserted into the visualizationlumen (335), permitting visualization of the treatment region. Ifpresent, the saline could be aspirated and the occlusion balloonsdeflated. Then, the OVC could be repositioned or removed. Thevisualization means (235) could be removed from the visualization lumen(335) at the user's convenience (e.g., between repositioning steps, atcompletion of the procedure, etc.).

The OVC may also be used as an agent-delivery catheter, wherein thesteps for delivering an agent would be the same as for the OPC, butwithout the steps involving the space-occupying balloon. Pressure topush the agent into the media of the vessel wall could be applied viathe agent delivery lumen (340).

For the reader's convenience, the following TABLE is provided, listingthe enumerated elements described above:

No. Description  10 Blood Vessel  20 Lumen  30 Occluded vessel lumen  40Occluded vessel lumen  50 Vessel endothelium  60 Targeted vessel segment100 Occlusion Perfusion Catheter (OPC) 105 Occlusion VisualizationCatheter (OVC) 110 Proximal End Adapter 120 Balloon inflation hub 125Balloon inflation/visualization & illumination means hub 130 Therapeuticagent perfusion/aspiration/guide wire hub  130a Therapeutic agentperfusion/aspiration/guide wire/pressure sensor hub 140 Distal End 150Catheter 160 5-lumen extruded catheter shaft 170 Longitudinal Axis 1803-Lumen catheter shaft between hubs (120) and (130) 190 3-Lumen cathetershaft between hubs (120) and (130), with sensor 192 5-lumen extrudedcatheter shaft, with sensor 200 Atraumatic tapered tip 202 Distalopening 210 Distal occlusion balloon 220 Aspiration segment 230 Spaceoccupying balloon 235 Visualization & illumination means 238 Output 240Therapeutic agent delivery segment 250 Proximal occlusion balloon 260Distal marker band 270 Proximal marker band 300 Guide wire lumen 310Occlusion balloon inflation lumen 320 Aspiration lumen (evacuatesdefined volume) 330 Space occupying balloon inflation lumen 335Visualization/illumination lumen 340 Therapeutic agent perfusion lumen(fills defined treatment volume) 380 Catheter exterior wall 390 Catheterinterior wall 410 Distal occlusion balloon inflation skive (catheterdistal end) 420 Aspiration (evacuate) skive (catheter distal end) 430Space occupying balloon inflation skive (catheter distal end) 435Visualization/illumination means slot 440 Perfusion (delivery) skive(catheter distal end) 450 Proximal occlusion balloon inflation skive(catheter distal end) 500 Guide wire port 510 Occlusion ballooninflation port (inflates both proximal & distal) 520 Aspiration(evacuation) port 530 Space occupying balloon inflation port 535Visualization means port 540 Therapeutic agent delivery (perfusion/fill)port 550 Fiber optic pressure sensor connector 610 Occlusion balloonshub inflation skive (catheter proximal end) 620 Aspiration (evacuation)hub skive (catheter proximal end) 630 Space occupying balloon hubinflation skive (catheter proximal end) 635 Visualization & illuminationmeans hub skive 640 Perfusion (fill) hub skive (catheter proximal end)700 First fiber optic pressure sensor 701 First fiber optic pressuresensor proximal end 702 First fiber optic pressure sensor distal end 704Second fiber optic pressure sensor 705 Second fiber optic pressuresensor proximal end 706 Second fiber optic pressure sensor distal end710 Two- or three-way valve or check valve

All references cited in this specification are herein incorporated byreference as though each reference was specifically and individuallyindicated to be incorporated by reference. The citation of any referenceis for its disclosure prior to the filing date and should not beconstrued as an admission that the present disclosure is not entitled toantedate such reference by virtue of prior invention.

It will be understood that each of the elements described above, or twoor more together may also find a useful application in other types ofmethods differing from the type described above. Without furtheranalysis, the foregoing will so fully reveal the gist of the presentdisclosure that others can, by applying current knowledge, readily adaptit for various applications without omitting features that, from thestandpoint of prior art, fairly constitute essential characteristics ofthe generic or specific aspects of this disclosure set forth in theappended claims. The foregoing embodiments are presented by way ofexample only; the scope of the present disclosure is to be limited onlyby the following claims.

1. A catheter comprising: a) a catheter shaft having a longitudinalaxis, a distal end having a shaft distal tip, and a proximal end; b) afirst balloon positioned on the shaft proximal to the shaft distal tip;c) a second balloon positioned on the shaft proximal to the firstballoon; d) a third balloon positioned on the shaft proximal to thesecond balloon; e) an agent delivery segment positioned on the shaftbetween the first and third balloons and having one agent deliverysegment orifice formed therein; f) an aspiration segment positioned onthe shaft between the first and third balloons and having one aspirationsegment orifice formed therein; and g) a guidewire lumen formed withinthe shaft and in communication with: an opening formed in a proximal endof the catheter; and an opening formed in a distal end of the catheterh) an agent delivery lumen in fluid communication with said agentdelivery segment orifice, and a first pressure-sensing means havingproximal and distal ends and a length therebetween extending throughsaid agent delivery lumen, wherein said first pressure sensing meansdistal end is at the agent delivery segment orifice or within the agentdelivery lumen, wherein said agent delivery segment orifice and saidaspiration segment orifice lie on opposite sides of said longitudinalaxis.
 2. The catheter of claim 1, wherein said first pressure-sensingmeans proximal end is in communication with a connector formed on theproximal end of the catheter shaft.
 3. The catheter of claim 1, furthercomprising a first inflation lumen in communication with the first andthird balloons.
 4. The catheter of claim 3, wherein said first inflationlumen is further in communication with a first balloon inflation portformed on the proximal end of the catheter shaft.
 5. The catheter ofclaim 1, further comprising a second inflation lumen in communicationwith the second balloon.
 6. The catheter of claim 5, wherein said secondinflation lumen is further in communication with a second ballooninflation port formed on the proximal end of the catheter shaft.
 7. Thecatheter of claim 1, further comprising an aspiration lumen incommunication with the aspiration segment orifice.
 8. The catheter ofclaim 7, wherein said aspiration lumen is further in communication withan aspiration port formed on the proximal end of the catheter shaft. 9.The catheter of claim 8, further comprising a valve in communicationwith said aspiration port.
 10. The catheter of claim 1, wherein saidagent delivery lumen is further in communication with an agent deliveryport formed on the proximal end of the catheter shaft.
 11. A cathetercomprising: a) a catheter shaft having a longitudinal axis, a distal endhaving a shaft distal tip, and a proximal end; b) a first balloonpositioned on the shaft proximal to the shaft distal tip; c) a secondballoon positioned on the shaft proximal to the first balloon; d) athird balloon positioned on the shaft proximal to the second balloon; e)an agent delivery segment positioned on the shaft between the first andthird balloons and having one agent delivery segment orifice formedtherein; f) an agent delivery lumen in communication with the agentdelivery segment orifice; g) an aspiration segment positioned on theshaft between the first and third balloons and having one aspirationsegment orifice formed therein; and h) a guidewire lumen formed withinthe shaft and in communication with: an opening formed in a proximal endof the catheter; and an opening formed in a distal end of the catheter;i) a first pressure-sensing means having proximal and distal ends and alength therebetween extending through said agent delivery lumen, whereinsaid first pressure-sensing means proximal end is in communication witha connector formed on the proximal end of the catheter shaft and saidfirst pressure-sensing means distal end is at the agent delivery segmentorifice or within the agent delivery lumen; and j) a secondpressure-sensing means having proximal and distal ends and a lengththerebetween extending through said agent delivery lumen, wherein saidsecond pressure-sensing means proximal end is in communication with theconnector formed on the proximal end of the catheter shaft and saidsecond pressure-sensing means distal end is located within the agentdelivery lumen; wherein said agent delivery segment orifice and saidaspiration segment orifice lie on opposite sides of said longitudinalaxis.
 12. A catheter comprising: a) a catheter shaft having alongitudinal axis, a distal end having a shaft distal tip, and aproximal end; b) a first balloon positioned on the shaft proximal to theshaft distal tip, a second balloon positioned on the shaft proximal tothe first balloon, and a third balloon positioned on the shaft proximalto the second balloon; c) a first inflation lumen in communication withthe first and third balloons, wherein said first inflation lumen isfurther in communication with a first balloon inflation port formed onthe proximal end of the catheter shaft; d) a second inflation lumen incommunication with the second balloon, wherein said second inflationlumen is further in communication with a second balloon inflation portformed on the proximal end of the catheter shaft; e) an agent deliverylumen, and an agent delivery segment positioned on the shaft between thesecond and third balloons and having one agent delivery segment orificeformed therein, wherein the agent delivery lumen is in communicationwith the agent delivery segment orifice and an agent delivery portformed on the proximal end of the catheter shaft; f) an aspirationlumen, and an aspiration segment positioned on the shaft between thefirst and second balloons and having one aspiration segment orificeformed therein, wherein the aspiration lumen is in communication withthe aspiration segment orifice and an aspiration port formed on theproximal end of the catheter shaft, said aspiration port optionallyfurther comprising a valve in communication with the aspiration port; g)a guidewire lumen formed within the shaft and in communication with anopening formed in a proximal end of the catheter and an opening formedin a distal end of the catheter; h) a first pressure-sensing meanshaving proximal and distal ends and a length therebetween extendingthrough said agent delivery lumen, wherein said first pressure-sensingmeans proximal end is in communication with a connector formed on theproximal end of the catheter shaft and said first pressure-sensing meansdistal end is at the agent delivery segment orifice or within the agentdelivery lumen; and i) a second pressure-sensing means having proximaland distal ends and a length therebetween, wherein said secondpressure-sensing means proximal end is in communication with theconnector formed on the proximal end of the catheter shaft and saidsecond pressure-sensing means distal end is located within the agentdelivery lumen, wherein said agent delivery segment orifice and saidaspiration segment orifice lie on opposite sides of said longitudinalaxis.